The purpose of this project is to determine the incidence rates, rates of progression, and risk factors for the chronic complications of type 2 diabetes. The study is conducted in the Pima Indians of the Gila River Indian Community, who have participated in a longitudinal epidemiologic study since 1965 (see project Z01 DK 69000). Risk factors for the major complications of diabetes, retinopathy, nephropathy, and coronary artery disease, are determined by longitudinal follow-up of diabetic subjects. Methods of ascertainment of these complications include fundus photography, measurement of urine albumin and serum creatinine concentrations, and electrocardiography. The incidence of diabetic nephropathy, as a function of duration of diabetes, was unrelated to age of onset of diabetes. Thus, risk of this complication is much more strongly related to characteristics of diabetes rather than age per se. By the time they reach middle adult years, Pima Indians with youth-onset diabetes have rates of advanced diabetes complications similar to those of older adults who have had diabetes for the same length of time. We are taking part in a multicentered genetic linkage study (Family Investigation of Nephropathy and Diabetes) of diabetic nephropathy in an attempt to identify susceptibility genes for nephropathy. As part of this collaboration, we identified informative ethnic-difference markers, i.e., genetic markers that distinguish between American Indian and European sources of heritage. These will be used in studying the genetics of nephropathy using the method of mapping by admixture linkage disequilibrium.